Clinico-pathological significance of immunohistochemically marked tumor-associated macrophage in classic Hodgkin lymphoma

Abstract

Background: Tumor-associated macrophages (TAM) are pivotal in remodeling of the tumor immune microenvironment and clinical outcome. Herein, we aim to evaluate the impact of immunohistochemical (IHC) expression of CD68 and CD163 in TAM on clinico-pathological features, patients' response to therapy and the overall survival (OS). Results: This retrospective study was performed on paraffin-embedded tissue blocks of 100 classic Hodgkin Lymphoma (cHL) cases diagnosed and treated at our Institution. Immunohistochemical scores of CD68 and CD163 were statistically related to bulky disease (p value = 0.005 for both), tumor stage (p value = 0.02 for both), International Prognostic Score (IPS) (p value = 0.04 and 0.02 respectively), and the overall response rate (ORR) (p value = 0.001). Additionally, CD163 was also statistically related to gender (p value = 0.02), serum albumin level (p value = 0.03), and B symptoms (p value = 0.04). HCV seropositivity did not relate to either CD68 or CD163 score. Using univariate analysis revealed that B symptoms, bulky disease, IPS ≥ 3, and CD163 > 25% were associated with lower OS (p values = 0.003, 0.006, 0.001, and < 0.001 respectively), while after multivariate cox regression analysis, B symptoms, IPS ≥ 3, and CD163 > 25% were related to inferior OS (p values 0.02, 0.02, and 0.003). Conclusion: CD163 expressing TAM is a powerful predictor for OS in cHL, unlike CD68.

Serum-Soluble CD163 Levels as a Prognostic Biomarker in Patients with Diffuse Large B-Cell Lymphoma Treated with Chemoimmunotherapy

“…This finding implies that elevated levels of soluble receptor CD163 may be a common feature among patients with DLBCL. In recent years, several studies have demonstrated the roles of TAMs and CD163 in the pathogenesis of hematopoietic malignancies including T-cell leukemia/lymphoma, acute myeloid leukemia, and classical Hodgkin lymphoma [ 17 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ]. In most studies, high CD163 expression was correlated with an inferior prognosis.…”

Macrophage-Based Therapeutic Strategies in Hematologic Malignancies

“…The lower level of M2 macrophages has been linked to a complete response and better survival [305]. The expressions of both TAM markers, CD68, and CD163 [306] are essential predictors of complete remission in CHL patients [307]. A high ratio of LAMs to Hodgkin-Reed-Sternberg cells at diagnosis is associated with a higher risk of CHL progression or death [308].…”